thromboplastin and Coronary-Stenosis

Changes in hemostasis after off-pump coronary artery bypass grafting are still being discussed. There is a lack of information about platelet activity and aspirin efficacy after coronary artery bypass grafting. The aim of this study was to assess and compare platelet activity and aspirin efficacy early and late after off-pump and on-pump coronary artery bypass grafting.. Eighty patients were enrolled in a prospective randomized study. Platelet activity was determined based on membrane expression of antigen CD62P (P-selectin) by means of flow cytometric analysis. Aspirin efficacy was assessed by using arachidonic acid-induced platelet aggregation. Blood samples were collected before the operation, immediately postoperatively, and on days 1, 2, 5, and 30.. In the off-pump group expression of P-selectin was markedly increased in comparison with preoperative values, with a maximum difference observed on day 2 (+53%, P = .02), and it was significantly higher compared with that seen in the on-pump group on days 2 and 5 (+53% vs +4%, P = .004, and +20% vs -16%, P = .005). On day 30, P-selectin expression was similar both between the groups and in comparison with the preoperative values. Arachidonic acid-induced platelet aggregation was gradually decreasing until day 30, but on day 2, there was an unexpected increase in aggregation that was more expressed in the off-pump group.. The platelet activity is higher in the early postoperative period in off-pump compared with on-pump coronary artery bypass grafting. The present aspirin strategy seems to be insufficient in the early postoperative period, irrespective of the surgical technique used.

Topics: Aged; Aspirin; Confidence Intervals; Coronary Artery Bypass; Coronary Artery Bypass, Off-Pump; Coronary Stenosis; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Graft Rejection; Graft Survival; Humans; Male; Middle Aged; P-Selectin; Platelet Activation; Platelet Aggregation; Platelet Count; Postoperative Care; Preoperative Care; Probability; Prognosis; Prospective Studies; Risk Assessment; Survival Analysis; Thromboplastin; Treatment Outcome

We investigated the safety and pharmacodynamics of escalating doses of recombinant nematode anticoagulant protein c2 (rNAPc2) in patients undergoing elective coronary angioplasty.. Recombinant NAPc2 is a potent inhibitor of the tissue factor/factor VIIa complex, which has the potential to reduce the risk of thrombotic complications in coronary artery disease.. In a randomized, double-blinded, dose-escalation, multicenter trial, 154 patients received placebo or rNAPc2 at doses of 3.5, 5.0, 7.5, and 10.0 microg/kg body weight as a single subcutaneous administration 2 to 6 h before angioplasty. All patients received aspirin, unfractionated heparin during angioplasty, and clopidogrel in case of stent implantation.. Minor bleeding rates for the doses 3.5 to 7.5 microg/kg were comparable to that with placebo (6.7%), whereas an incidence of 26.9% was observed at the 10.0 microg/kg dose level (p < 0.01). Major bleedings occurred in the 5.0 microg/kg (n = 3) and 7.5 microg/kg (n = 1) dose groups. The three patients in the 5.0 microg/kg dose group also received a glycoprotein IIb/IIIa receptor inhibitor at the moment of major bleeding. Systemic thrombin generation, as measured by prothrombin fragment 1+2 (F(1+2)), was suppressed in all rNAPc2 dose groups to levels below pretreatment values for at least 36 h. In the placebo group, a distinct increase of F(1+2) levels was observed following cessation of heparin.. Inhibition of the tissue factor/factor VIIa complex with rNAPc2, at doses up to 7.5 microg/kg, in combination with aspirin, clopidogrel, and unfractionated heparin appears to be a safe and effective strategy to prevent thrombin generation during coronary angioplasty.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Coronary Stenosis; Coronary Thrombosis; Dose-Response Relationship, Drug; Double-Blind Method; Elective Surgical Procedures; Factor VIIa; Female; Helminth Proteins; Humans; Male; Middle Aged; Postoperative Complications; Thromboplastin

A different rate and timing of subacute stent thrombosis after percutaneous coronary intervention was reported with various peri-interventional antithrombotic regimens. Next to platelet activation, coagulation triggered by tissue factor (TF) may play a key role in this process. Thirty-one consecutive patients with stable and unstable angina undergoing coronary stenting were randomly assigned to adjunct oral anticoagulation/anti-platelet therapy (coumadin, dipyridamole, aspirin and heparin; n = 16) or adjunct anti-platelet therapy with thienopyridin (ticlopidine, aspirin and heparin; n = 15). Antigen levels of plasma TF, total tissue factor pathway inhibitor (TFPI) and TFPI/ activated factor X (TFPI/FXa) complex were determined before and for up to 6 days after intervention by immunoassay. At baseline, significantly higher levels of plasma TF and TFPI/FXa were found in patients with unstable angina [TF, 161 pg/ml (126-191 pg/ml); TFPI/FXa, 7.8 ng/ml (6.1-9.6 ng/ml)] compared with stable angina [TF, 62 pg/ml (46-82 pg/ml), P < 0.0001; TFPI/FXa, 4.5 ng/ml (3-7.6 ng/ml), P= 0.003]. One hour after intervention, an increase of plasma TF and TFPI/FXa was seen in both treatment groups. In unstable angina patients, plasma levels of TF, TFPI and TFPI/FXa were more efficiently reduced by adjunct ticlopidine therapy compared with adjunct coumadin/dipyridamole. These data suggest reduced release of circulating TF by combined anti-platelet therapy with ticlopidine and aspirin after coronary artery stenting, which may-contribute to the lower incidence of subacute stent thrombosis previously observed.

Topics: Adult; Angina Pectoris; Angina, Unstable; Angioplasty, Balloon, Coronary; Anticoagulants; Aspirin; Coronary Angiography; Coronary Stenosis; Dipyridamole; Dose-Response Relationship, Drug; Drug Therapy, Combination; Enzyme-Linked Immunosorbent Assay; Factor Xa; Female; Follow-Up Studies; Hemorrhage; Heparin; Humans; Lipoproteins; Male; Middle Aged; Statistics as Topic; Stents; Thromboplastin; Thrombosis; Ticlopidine; Time Factors; Warfarin

FFR-rFVIIa is an inactivated recombinant factor VIIa (rFVIIa) that inhibits the binding of factor VIIa to tissue factor (TF). It has been shown to prevent TF-induced thrombosis in animals. The present study is a substudy of the Active Site Inhibited Seven (ASIS) trial and examines the antithrombotic effect of 3 doses of FFR-rFVIIa in 24 patients undergoing percutaneous coronary intervention (PCI). Group 1 (n=9) received 400 microg/kg FFR-rFVIIa and 40 to 50 U/kg heparin, group 2 (n=7) received 200 microg/kg FFR-rFVIIa and 100 U/kg heparin, and group 3 (n=8) received 50 microg/kg FFR-rFVIIa and 100 U/kg heparin. Blood thrombogenicity was assessed as total thrombus area and fibrin deposition on the perfusion chamber at shear rate conditions typical of mild-moderate coronary stenosis. Baseline blood thrombogenicity was evaluated a day before PCI, after heparin administration. A second perfusion chamber study was performed just before PCI, 15 minutes after the administration of heparin and FFR-rFVIIa. Thrombus formation at a high shear rate was markedly reduced in groups 1 and 2 after drug administration, by 79% to 84% and 76% to 87%, respectively (P<0.004 [group 1], P<0.04 [group 2]). In group 3, moderate thrombus reduction of 46% to 48% was achieved (P<0.04). Fibrin deposition in all 3 groups was nearly eliminated after drug administration. Our data demonstrate that FFR-rFVIIa has a potent antithrombotic effect at different shear rates and severe arterial injury conditions.

Topics: Angioplasty, Balloon, Coronary; Animals; Blood Coagulation Tests; Coronary Stenosis; Double-Blind Method; Drug Administration Schedule; Factor VIIa; Female; Fibrin; Fibrinolytic Agents; Humans; Injections, Intravenous; Male; Middle Aged; Perfusion; Platelet Function Tests; Recombinant Fusion Proteins; Swine; Thromboplastin; Thrombosis

Stent implantation into atherosclerotic coronary arteries releases particulate debris and soluble substances that contribute to impaired microvascular perfusion. Here we addressed the potential for microvascular obstruction in patients with stenotic native right coronary arteries (nRCA) compared with saphenous vein grafts on right coronary arteries (SVG-RCA). We enrolled symptomatic, male patients with stable angina pectoris and a flow-limiting stenosis in their nRCA or SVG-RCA (n = 18/18). Plaque volume and composition were analyzed using intravascular ultrasound before stent implantation. Coronary aspirate was retrieved during stent implantation under protection with a distal occlusion/aspiration device and divided into particulate debris and plasma. The release of catecholamines, endothelin, serotonin, thromboxane B2, and tumor necrosis factor-α was measured. The response of rat mesenteric arteries with intact (+E) and denuded (-E) endothelium to aspirate plasma (without and with selective endothelin receptor blockade) was normalized to that by potassium chloride (KClmax = 100%). Plaque volume and composition were not different between nRCA and SVG-RCA. There was less particulate debris (65 ± 8 vs. 146 ± 23 mg; P < 0.05) and more endothelin release (5.8 ± 0.8 vs. 1.3 ± 0.7 pg/ml; P < 0.05) in nRCA than in SVG-RCA, whereas the release of the other mediators was not different. Aspirate from nRCA induced stronger vasoconstriction than that from SVG-RCA [nRCA, 78 ± 6% (+E)/84 ± 5% (-E); SVG-RCA, 59 ± 6% (+E)/68 ± 3% (-E); P < 0.05 nRCA vs. SVG-RCA], which was attenuated by a nonspecific endothelin and a specific endothelin receptor A antagonist. Thus coronary aspirate from stented nRCA is characterized by less debris but more endothelin and stronger vasoconstrictor response than that from SVG-RCA.

Topics: Aged; Angina, Stable; Animals; Coronary Stenosis; Endothelins; Epinephrine; Graft Occlusion, Vascular; Humans; Male; Mesenteric Arteries; Middle Aged; Norepinephrine; Rats; Saphenous Vein; Serotonin; Stents; Thromboplastin; Thromboxane B2; Tumor Necrosis Factor-alpha; Vasoconstriction

Tissue factor (TF) and its specific inhibitor, tissue factor pathway inhibitor (TFPI), are important contributors to the initiation of the coagulation process.. To compare plasma levels of soluble TF (sTF) and free-TFPI (f-TFPI) between patients with stable angina pectoris (SAP) and acute coronary syndrome (ACS) and to assess the impact of the two variables on long-term prognosis.. Patients with SAPs (n = 1146) and acute coronary syndrome (n = 523) from the AtheroGene study were included and followed for 2.3 years. Because of the strong impact of unfractionated heparin (UFH) on f-TFPI levels, but not on sTF levels, patients having received UFH before blood drawing were excluded from the analyses on f-TFPI (n = 226).. On admission, no significant differences in sTF levels were observed between SAP and ACS patients. By comparison to patients with stable angina, f-TFPI levels significantly increased in patients with acute unstable angina and further increased in patients presenting with non-ST-elevation myocardial infarction and ST-elevation myocardial infarction (P < 10(-4)). Among the 1669 individuals with a coronary artery disease, 56 died from a cardiovascular cause. In prospective analyses, high sTF levels were independently associated with an increased risk of cardiovascular death in individuals with ACS (fully adjusted hazard ratio associated with one quartile increase = 2.06; 95% confidence interval 1.24-3.45; P = 0.006) but not in those with SAP (hazard ratio = 1.07; 95% confidence interval 0.78-1.46; P = 0.67). In SAP and ACS patients, high f-TFPI levels were not independently associated with an increased risk of cardiovascular death.. Plasma sTF levels were predictive of cardiovascular mortality in individuals with ACS, whereas f-TFPI levels were associated with the severity of myocardial damage on admission but were not independently related to outcome.

Topics: Aged; Angina Pectoris; Biomarkers; Cardiovascular Diseases; Cohort Studies; Coronary Stenosis; Female; Follow-Up Studies; Germany; Humans; Lipoproteins; Male; Middle Aged; Myocardial Infarction; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Prospective Studies; Risk Assessment; Severity of Illness Index; Syndrome; Thromboplastin; Time Factors

Monocytes and macrophages synthesize tissue factor (TF) which plays a role in thrombogenicity in coronary artery disease. This study was conducted to investigate the effect of Rho/Rho-kinase inhibition on the synthesis of TF in cultured human monocytes. 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins), C3 exoenzyme and Rho-kinase inhibitors were added to isolated peripheral blood monocytes and the synthesis of TF was assessed by reverse transcriptase polymerase chain reaction (RT-PCR), Western blotting and immunohistochemistry. Rho activity was determined by measuring the GTP-bound form of Rho A. Cerivastatin and pravastatin reduced the levels of TF antigen and mRNA. The suppressive effect of statins on TF synthesis was reversed by geranylgeranylpyrophosphate (GGPP) and the restoring effect of GGPP was eliminated by C3 exoenzyme and Y-27632. Pravastatin decreased the activity of Rho A, suggesting that the suppression of TF synthesis by statins is mediated via inhibition of the geranylgeranylation of Rho. Moreover, inhibition of Rho and Rho-kinase downregulated the synthesis of TF. Our results suggest that Rho/Rho-kinase signaling is involved in the synthesis of TF in human monocytes and that inhibition of Rho/Rho-kinase may be useful for treating thrombogenicity in coronary artery disease.

Topics: Acyl Coenzyme A; Analysis of Variance; Base Sequence; Blotting, Western; Cells, Cultured; Coronary Stenosis; Down-Regulation; Humans; Immunohistochemistry; Intracellular Signaling Peptides and Proteins; Leukocytes, Mononuclear; Molecular Sequence Data; Pravastatin; Probability; Protein Serine-Threonine Kinases; Pyridines; Reverse Transcriptase Polymerase Chain Reaction; rho-Associated Kinases; RNA, Messenger; Sensitivity and Specificity; Thromboplastin

Platelet activation is known to participate to the pathogenesis of acute coronary syndromes. Aminophospholipid exposure and microparticles shedding are hallmarks of full platelet activation and may account for the dissemination of prothrombotic seats. Using flow cytometry analysis of annexin V binding to externalized aminophospholipids, we followed platelet procoagulant activity (PPA) and platelet microparticles (PMP) shedding in venous and coronary whole blood samples from 30 patients with unstable angina before and after percutaneous coronary angioplasty (PTCA) and stent implantation. Baseline values of PPA and PMP were significantly more elevated in patients than in control subjects (p < 0.005). PMP percentage was significantly higher in coronary than in venous blood, and in coronary blood of patients with proximal instead of mid/distal lesions of coronary arteries. No enhancement of platelet reactivity to TRAP and collagen was induced by procedure. Whereas activated GpIIb-IIIa and P-selectin expression decreased 24 h and 48 h after procedure, PPA and PMP remained as elevated as before. Thus, flow cytometry is a reliable method for detection of fully activated platelets in whole blood samples. Annexin V binding analysis demonstrates the persistance of in vivo platelet activation, despite the use of antiaggregating agents.

Topics: Aged; Angina, Unstable; Angioplasty, Balloon, Coronary; Annexin A5; Biomarkers; Collagen; Combined Modality Therapy; Comorbidity; Coronary Angiography; Coronary Stenosis; Coronary Vessels; Diabetes Mellitus; Female; Flow Cytometry; Humans; Hypercholesterolemia; Male; Middle Aged; Obesity; P-Selectin; Platelet Activation; Platelet Count; Platelet Glycoprotein GPIIb-IIIa Complex; Proteins; Receptors, Thrombin; Risk Factors; Stents; Thromboplastin; Veins